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Original research
Influenza vaccination in patients with heart failure: a systematic review and meta-analysis of observational studies
  1. Bárbara Sucena Rodrigues1,
  2. Cláudio David2,
  3. João Costa2,3,
  4. Joaquim J Ferreira2,3,
  5. Fausto J Pinto4,5,
  6. Daniel Caldeira2,4,5
  1. 1 Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  2. 2 Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  3. 3 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  4. 4 Faculdade de Medicina, Centro Cardiovascular da Universidade de Lisboa (CCUL), Centro Académico Médico de Lisboa (CAML), Universidade de Lisboa, Lisboa, Portugal
  5. 5 Cardiology Department, Hospital Santa Maria / Santa Maria University Hospital - Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisboa, Portugal
  1. Correspondence to Professor Daniel Caldeira, CCUL, Faculdade de Medicina da Universidade de Lisboa, Lisboa 1649-028, Portugal; dgcaldeira{at}


Objective Despite the progression of treatments over decades, heart failure (HF) is a disease with high morbidity, mortality and economic burden. Influenza infection is an important trigger for cardiovascular (CV) events, including HF. Influenza vaccination has been seen to reduce the risk of CV mortality in patients with coronary disease, but the effect in patients with HF is still unclear. Therefore, we conducted a systematic review to evaluate the effect of influenza vaccination in the morbimortality of patients with HF.

Methods MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Technology Assessment and PsycINFO databases (December 2018) were searched for longitudinal studies evaluating influenza vaccination compared with a non-vaccination control group in patients with HF. The risk of bias was assessed according to the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled HRs with 95% CIs, and heterogeneity was evaluated using the I2 statistics.

Results Six cohort studies evaluating 179 158 patients with HF were included in the meta-analysis. Influenza vaccination was associated with a lower risk of all-cause mortality (HR=0.83; 95% CI 0.76 to 0.91; I2=75%). The effect of the influenza vaccination was not statistically significant in a pooled analysis of CV mortality (HR=0.92, 95% CI 0.73 to 1.15; 2 studies) and of all-cause hospitalisations (HR=1.01, 95% CI 0.92 to 1.11; 2 studies). The majority of outcomes in the included studies had a serious risk of bias and almost all evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence.

Conclusions Influenza vaccination was associated with a significant decrease in all-cause mortality risk in patients with HF.

  • Flu
  • Coryza
  • Influenza
  • Vaccine
  • heart failure

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  • Contributors DC and BSR contributed to the concept and design of the study and extraction, analysis and interpretation of the data, wrote the first draft of the manuscript, critically revised the manuscript, and gave final approval of the submitted manuscript. CD contributed to the concept and design of the study and interpretation of the data, critically revised the manuscript, and gave final approval of the submitted manuscript. JC, JJF and FJP contributed to interpretation of data, critically revised the manuscript and gave final approval of the submitted manuscript.

  • Funding statement The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme; FJP had consultant and speaker fees with Astra Zeneca, Bayer, BMS, Boehringer Ingelheim and Daiichi Sankyo. DC has participated in educational meetings and/or attended conferences or symposia with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche.

  • Patient and public involvement statement This research was done without patient involvement. Patients were not invited to comment on the study design and were not consulted to develop patient relevant outcomes or interpret the results. Patients were not invited to contribute to the writing or editing of this document for readability or accuracy.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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